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Biomedical subjects

A Singer

Publications and source records attributed to A Singer.

At least 235 records · Page 13Linked to original sources

Management of squamous atypia (borderline nuclear abnormalities): repeat cytology or colposcopy?

A prospective cytological, colposcopic and histological study was conducted in 44 women with cervical cytology showing borderline nuclear abnormalities insufficient for the diagnosis of dyskaryosis. Atypical squamous epithelium was found on colposcopy in 41 patients and cervical intraepithelial neoplasia (CIN) was diagnosed on histology in 33 patients (75%) including 10 with CIN 3. Repeat cytology obtained under colposcopic vision was negative in 12 (33.4%) patients with CIN. The high prevalence of CIN in smears showing only borderline nuclear abnormalities and the high false negative rate of repeat cytology indicate that colposcopy should be the first line of management for these patients.

Adult↗

Recognition requirements for the activation, differentiation and function of T-helper cells specific for class I MHC alloantigens.

The present review has focused on the specificity of the T-helper cell populations initiating MHC class I alloreactions. In contrast to conventional immune responses against soluble antigens, responses against membrane-bound class I alloantigens are initiated by two distinct antigen-specific T-helper cell populations that can be distinguished by their Lyt phenotype, MHC restriction specificity, antigen specificity, and requirement for thymically determined self-recognition. Alloresponses were shown to be a composite consisting of two distinct components: one mediated by L3T4+ Th cells and very similar to conventional self + X responses; and one mediated by Lyt2+ Th cells and unique to alloresponses against MHC class I antigens. As would befit an unusual Th cell population, the recognition/response spectrum of Lyt2+ Th cells was highly unusual and was found to be the basis for much of the uniqueness we attribute to immune alloreactions, including rapid rejection of tissue allografts in vivo.

Animals↗

An investigation of patients presenting with multiple physical complaints using the illness behaviour questionnaire.

The Illness Behaviour Questionnaire was used to determine whether three groups of patients who had presented with multiple symptoms in different treatment settings (Briquet's syndrome, post-viral fatigue syndrome, and a heterogeneous general practice group) could be differentiated from one another and from a mixed group of psychiatric patients on the basis of their abnormal illness behaviour. All groups completed a version of the Perley and Guze diagnostic criteria for Briquet's syndrome. The three groups presenting with multiple symptoms were more similar to each other than to the psychiatric patients. The results suggest that patients presenting with multiple symptoms include similar populations of patients who are poorly distinguished using current schemes of classification.

Adult↗

Evoked response potentials and regional cerebral blood flow in somatization disorder.

Somatization disorder (SMD) is a chronic condition characterized by multiple complaints which are not due to any apparent organic illness but frequently involve pain. This study employs computer-aided imaging technologies to examine brain function in thousandths of a second (event-related brain potentials) and over a number of minutes (regional cerebral blood flow). Fourteen patients with SMD and 14 normal controls were investigated. Results from both studies suggest that patients with SMD have a dysfunction in the processes of attention, compared to normal controls.

Adult↗

Recognition of cervical neoplasia by the estimation of a free-radical reaction product (octadeca-9,11-dienoic acid) in exfoliated cells.

The molar ratio between a diene-conjugated linoleic-acid isomer (18:2(9,11)) and the parent linoleic acid (18:2(9,12)), both esterified as phospholipids, was significantly different in exfoliated cells from normal cervices and from cervices with colposcopic and cytological evidence of precancer. The measurement may provide a simple and perhaps improved alternative to cytological screening.

Biomarkers, Tumor↗

Quantitative deoxyribonucleic acid analysis of patients with mild cervical atypia: a potentially malignant lesion?

Quantitative deoxyribonucleic acid (DNA) analysis of cervical biopsy material from 32 women with cytologic, colposcopic, and histologic evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia I, reactive atypia, or human papillomavirus infection was carried out using flow cytometry and Feulgen microspectrophotometry. Evidence of aneuploidy, ie, neoplastic transformation, was demonstrated in all cases of cervical intraepithelial neoplasia I and 68% of cases with human papillomavirus-induced atypia. These results support the growing impression that human papillomavirus-induced cervical atypia should be regarded as a true precursor of cervical neoplasia, and emphasize the necessity to refer patients with mild atypia for definitive diagnosis and management.

Carcinoma in Situ↗

Recognition of MHC class I allodeterminants regulates the generation of MHC class II-specific CTL.

We have analyzed the signals influencing the generation of major histocompatibility complex (MHC) class II allospecific cytolytic T lymphocytes (CTL) and have found that the development of these CTL is actively regulated in primary in vitro cultures by Lyt-2+ T cells triggered in response to MHC class I alloantigens. Class II allospecific CTL can be readily stimulated in primary cultures, but the presence of a simultaneous class I MHC stimulus in these cultures causes a marked reduction of class II-specific CTL activation. This reduction can be prevented by adding to culture a dose of monoclonal anti-Lyt-2 antibody (in the absence of complement) that does not block the generation of class I-specific CTL. The role of MHC class I alloantigens in the regulation of class II allospecific responses illustrates that T cells recognizing class I and class II MHC antigens in mixed leukocyte cultures interact in a complex and nonreciprocal manner to influence the final effector T cell repertoire elicited by this complex immunogenic challenge.

Animals↗

Differential helper and effector responses of Lyt-2+ T cells to H-2Kb mutant (Kbm) determinants and the appearance of thymic influence on anti-Kbm CTL responsiveness.

The goal of this study was to assess and compare the allorecognition requirements for eliciting Lyt-2+ helper and effector functions from primary T cell populations. By using interleukin 2 (IL 2) secretion as a measure of T helper (Th) function, and cytolytic T lymphocyte (CTL) generation as a measure of effector function, this study compared the responses of Lyt-2+ T cells from wild-type B6 mice against a series of H-2Kb mutant determinants. Although all Kbm determinants stimulated B6 Lyt-2+ T cells to become cytolytic effector cells, the various Kbm determinants differed dramatically in their ability to stimulate Lyt-2+ T cells to function as IL 2-secreting helper cells. For example, in contrast to Kbm1 determinants that stimulated both helper and effector functions, Kbm6 determinants only stimulated B6 Lyt-2+ T cells to become cytolytic and failed to stimulate them to secrete IL 2. The distinct functional responses of Lyt-2+ T cells to Kbm6 determinants was documented by precursor frequency determinations, and was not due to an inability of the Kbm6 molecule to stimulate Lyt-2+ Th cells to secrete IL 2. Rather, it was the specific recognition and response of Lyt-2+ T cells to novel mutant epitopes on the Kbm6 molecule that was defective, such that anti-Kbm6 Lyt-2+ T cells only functioned as CTL effectors and did not function as IL 2-secreting Th cells. The failure of Lyt-2+ anti-Kbm6 T cells to function as IL 2-secreting Th cells was a characteristic of all Lyt-2+ T cell populations examined in which the response to novel mutant epitopes could be distinguished from the response to other epitopes expressed on the Kbm6 molecule. The absence of significant numbers of anti-Kbm6 Th cells in Lyt-2+ T cell populations was examined for its functional consequences on anti-Kbm6 CTL responsiveness. It was found that primary anti-Kbm6 CTL responses could be readily generated in vitro, but unlike responses to most class I alloantigens that can be mediated by Lyt-2+ Th cells, anti-Kbm6 CTL responses were strictly dependent upon self-Ia-restricted L3T4+ Th cells. Because the restriction specificity of L3T4+ Th cells is determined by the thymus, in which their precursors had differentiated, anti-Kbm6 CTL responsiveness, unlike responsiveness to most class I alloantigens, was significantly influenced by the Ia phenotype of the thymus in which the responder cells had differentiated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Progressive potential of mild cervical atypia: prospective cytological, colposcopic, and virological study.

A prospective study of 100 women with cytological and colposcopic evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia (CIN) grade I was started in October, 1983. 26% of early preinvasive cervical lesions progressed to histologically proven CIN III. Spontaneous regression of mild cervical atypia occurred in only 11 cases, and in 4 of these CIN recurred. The overall prevalence of human papillomavirus type 16 (HPV 16) in the study group, detected by filter DNA-DNA hybridisation of a cervical cytological specimen, was 39%. However, 22 of the 26 (85%) cases of progressive disease were positive for HPV 16. Detection of HPV 16 may be a non-invasive way of identifying women at high risk of rapid progression of mild cervical atypia to CIN III.

Adult↗

Characterization of two distinct primary T cell populations that secrete interleukin 2 upon recognition of class I or class II major histocompatibility antigens.

This study has characterized the primary T cell subpopulations that secrete IL-2 in response to recognition of either class I or class II MHC encoded determinants. The addition to culture of anti-IL-2-R mAb inhibited the consumption of IL-2 by activated lymphocytes during the response period, permitting a much more accurate assessment of the amount of IL-2 produced in the response cultures. Using this response system, we found that primary T cell populations contain two IL-2-secreting T cell subsets that express reciprocal phenotypes and different MHC recognition specificities: an L3T4+, Lyt-2- T cell subset responsive to both class I and class II MHC alloantigens, and an L3T4-Lyt-2+ T cell subset responsive only to class I MHC alloantigens. The L3T4+ T cell subset expressed a broad functional response repertoire in that L3T4+ T cells were triggered to secrete IL-2 upon recognition of unmodified self-Ia determinants, allogeneic Ia determinants, and class I alloantigens presented by self-Ia determinants. The activation of L3T4+ IL-2-secreting T cells, even those responsive to class I MHC alloantigens, could be blocked completely by anti-Ia mAbs, confirming that the L3T4+ T cell subset was in fact class II restricted. In contrast, the Lvt-2+ T cell subset expressed a narrow functional response repertoire in that they were triggered to secrete IL-2 only in response to allogeneic class I MHC determinants, and were not triggered to secrete IL-2 even in response to TNP-modified self-MHC determinants. The specificity of Lyt-2+ IL-2-secreting T cells for class I MHC allodeterminants was confirmed by the observations that: (a) their activation could be blocked completely by anti-class I mAbs, (b) they could be triggered by Ia- cell lines which expressed class I MHC alloantigens and possessed accessory function, and (c) they responded to class I MHC alloantigens but failed to respond to class II MHC alloantigens, even in the presence of exogenously added second signals that circumvented the requirement for alloantigen-bearing accessory cells. Finally, the frequency of primary Lyt-2+ T cells that secreted IL-2 in response to class I (Kbm1) MHC alloantigens was shown to be only minimally lower than that of L3T4+ T cells that secreted IL-2 in response to class II (I-Abm12) MHC alloantigens.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Regulation of T15 idiotype dominance. III. Phosphocholine-specific B-cell activation in vivo requires major histocompatibility complex-restricted T-cell help.

We have examined the requirement for major histocompatibility complex (MHC)-restricted T-cell help in the secondary in vivo antibody response to phosphocholine (PC). The memory response to PC has been demonstrated previously to be comprised of T15-dominant IgM and IgG3 plaque-forming cells (PFC) derived primarily from the Lyb-5+ B-cell subset, and IgG1 and IgG2 PFC, few of which bear the T15 idiotype and are predominantly derived from the Lyb-5- B-cell subset. Using carrier-primed (A X B)F1 T cells which have matured in a parentA chimeric environment so that "self" recognition is of the MHC determinants of parentA but not parentB, we have found that parentA PC-primed B cells, but not parentB PC-primed B cells, are activated. Even in the presence of an ongoing parentA anti-PC response, parentB PC-primed B cells were not activated, indicating that the restriction was between the helper T cell and the B cell, not between T-helper and accessory cells. MHC-restricted T-cell help was required by B cells producing T15+ and T15- IgM, IgG3, IgG1, and IgG2 responses.

Animals↗